Daunorubicin is biotransformed anaerobically by rat liver microsomes with a reduced nicotinamide adenine dinucleotide phosphate-generating system to form a series of aglycones. The first reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7-deoxyaglycone, is followed by reduction of the C-13 keto group. The 7-hydroxyaglycone may also form by hydrolytic cleavage of the amino sugar followed then by the same C-13 keto reduction. These reactions are not inhibited by β-diethylaminoethyldiphenylpropyl acetate, whereas subsequent reactions in the D ring of the aglycones can be completely blocked by this cytochrome P-450 inhibitor: reductive and hydrolytic cleavage of the C-4 methoxy group. Thus, five reactions at three sites are described and theoretical pathways are proposed for the expected 12 aglycones from daunorubicin.


This project was supported in part by Project Grant CA-24778 from the National Cancer Institute and by a grant from the Gunnar Nilsson Cancer Research Fund.

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